Cellular and molecular basis of progesterone-induced neuroprotection

Progesterone exerts several effects in the central nervous system not directly involved in reproduction or sex behavior. Non-reproductive effects are better observed under pathological conditions, and include stimulation of myelin formation, neurogenesis and neurosteroidogenesis, preserved mitochondrial function, neuroprotection, anti-inflammatory effects, decreased glutamate excitotoxicity, and regulation of mood, memory and cognition. In addition, the progesterone reduced derivative allopregnanolone shows anxiolytic, sedative and anesthetic properties after binding to GABAa receptors. In the present report we provide examples of [1] progesterone effects on the local synthesis of steroids (“neurosteroids”) in a demyelination model, [2] the requirement of the classical progesterone receptor for the antiinflammatory effects in mice with spinal cord injury, and [3] the protective role of progesterone and allopregnanolone in a mouse model of neurodegeneration. In conclusion, the beneficial effects observed in different experimental paradigms support the versatile properties of progesterone in animal models of central nervous system disorders.La progesterona produce varios efectos en el sistema nervioso central no relacionados a la reproducción o comportamiento sexual. Estos efectos adicionales se observan preferentemente bajo condiciones patológicas, e incluyen la estimulación de la formación de mielina, la neurogenesis y neuroesteroidogenesis, el mantenimiento de la función mitocondrial, efectos anti-inflamatorios, disminución de la excitotoxicidad del glutamato y regulación del humor, memoria y conocimiento. En agregado, el derivado reducido de progesterona – alopregnanolona – muestra propiedades ansiolíticas, sedantes y anestésicas luego de su unión al receptor GABAa. Este Minireview detalla los efectos de progesterona sobre [1] la síntesis local de esteroides (“neuroesteroides”), en un modelo de desmielinizacion, [2] ejemplifica el requerimiento del receptor clásico de progesterona para los efectos anti-inflamatorios en un modelo de injuria espinal en ratón, y finalmente [3] discute el rol protector de la progesterona y de la alopregnanolona en un modelo murino de degeneración de motoneurona. Como conclusión, los efectos beneficiosos mostrados en diferentes paradigmas experimentales apoyan las propiedades versátiles de la progesterona en modelos de patologías del sistema nervioso central.Sociedad Argentina de Fisiologí

Nutritional valuation of schoolchildren from three Ibero-American countries: A comparative analysis of the references proposed by International Obesity Task Force (IOTF) and World Health Organization (WHO)

Introducción: El índice de masa corporal (IMC) resulta un indicador útil para valorar la condición nutricional en la infancia y adolescencia. Si bien no existe consenso respecto a los valores o puntos de corte de IMC que deben utilizarse para la diagnosis del sobrepeso, la obesidad o la insuficiencia ponderal, las referencias propuestas por la Organización Mundial de la Salud (OMS) y la International Obesity Task Force (IOTF) son las más aceptadas. No obstante, existen discrepancias importantes en los resultados obtenidos en función de una u otra referencia. Objetivo: Analizar y comparar la condición nutricional de una muestra internacional a partir del IMC, mediante la aplicación simultánea de las referencias recomendadas por la IOTF y la OMS. Métodos: Se calculó el IMC de 1289 escolares de 10 a 13 años de México, Venezuela y España. A cada niño le fue atribuida una categoría nutricional (bajo peso, normopeso, sobrepeso y obesidad) utilizando el criterio de la IOTF (puntos de corte equivalentes a 18,5; 25 y 30 en adultos) y OMS (-1 DE: bajo peso + 1 DE: sobrepeso y +2 DE: obesidad). Las prevalencias de estado nutricional obtenidas por cada criterio fueron comparadas mediante la prueba de Chi-Cuadrado. Resultados: El porcentaje de escolares en cada una de las categorías nutricionales varió significativamente en función de la referencia empleada. La prevalencia de malnutrición por exceso o por defecto fue, en ambos sexos y en los tres países, superior al emplear los parámetros OMS. La referencia OMS evidenció un 10,9% menos de niños normonutridos y un 13,1% más de malnutridos que la IOTF. Discusión: Los resultados de esta investigación permiten inferir que la referencia propuesta por la OMS resulta ser más “preventiva” al momento de identificar individuos malnutridos. Se subraya la importancia de especificar los criterios empleados para la determinación del estado nutricional en los estudios de carácter epidemiológico, así como de contrastar las referencias empleadas para el diagnóstico. Conclusiones: Las referencias OMS para IMC sobrestiman la prevalencia de bajo peso, sobrepeso y obesidad en relación a los puntos de corte propuestos por el IOTF para el diagnóstico de la malnutrición.Introduction: Body Mass Index (BMI) is a useful tool for assessing nutritional status in childhood and adolescence. Although there is no consensus on BMI values or cutoffs to be used for the diagnosis of overweight, obesity and underweight references proposed by World Health Organization (WHO) and International Obesity Task Force (IOTF) are the most accepted. However, there are significant discrepancies in the results obtained in terms of either reference. Objective: To analyze and compare the nutritional status of an international sample from IMC, by simultaneous application of IOTF and WHO recommended references. Methods: 1289 schoolchildren’s BMI between 10 and 13 years of Mexico, Venezuela and Spain was estimated. Each child was assigned a nutritional category (underweight, normal weight, overweight and obese) using the IOTF criteria (points cut equivalent to 18,5, 25 and 30 in adults) and WHO (-1 SD: low weight +1 DE: overweight and +2 SD: obesity). The prevalence of nutritional status of each criterion was compared using the Chi-square test. Results: The percentage of students in each of the nutritional categories mottled significantly depending on the reference used. The prevalence of excess or defect malnutrition, in both sexes and in all three countries, was exceeded using the WHO parameters. WHO reference showed 10,9% less than well-nourished children and 13,1 % more malnourished than the IOTF. Discussion: The results of this research allow inferring that the reference proposed by WHO appears to be more “protecting” when identifying malnourished individuals. The importance of specifying the criteria for determination of nutritional status in epidemiologic studies, as well as to contrast the references used for diagnosis, is emphasized. Conclusions: The WHO BMI references overestimate the prevalence of underweight, overweight and obesity in relation to the cutoff points proposed by the IOTF for diagnosing malnutrition.Fil: Bergel Sanchís, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Cesani Rossi, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Cordero, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucuman. Instituto Superior de Estudios Sociales; ArgentinaFil: Navazo, Bárbara. Universidad Nacional de la Plata. Facultad de Cs.naturales y Museo. Departamento Científico de Antropología. Cátedra de Antropología Biológica Iv; ArgentinaFil: Olmedo, S.. Programa de Ecología Reproductiva del Gran Chaco Argentino. Formosa; ArgentinaFil: Quintero, F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de la Plata. Facultad de Cs.naturales y Museo. Departamento Científico de Antropología. Cátedra de Antropología Biológica Iv; ArgentinaFil: Sardi, Marina Laura. Universidad Nacional de la Plata. Facultad de Cs.naturales y Museo. Departamento de Antropología; ArgentinaFil: Torres, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras; ArgentinaFil: Arechiga, J.. Universidad Nacional Autónoma de México; MéxicoFil: Méndez de Pérez, B. Universidad Nacional de Venezuela; VenezuelaFil: Marrodán, M. D.. Universidad Complutense de Madrid; Españ

Taking tadpole biology into the 21st century: a consensus paper from the First Tadpoles International Workshop

Although tadpoles are common, frequently encountered vertebrates, their natural history is poorly known. Despite the fact that Brazil harbors the highest anuran diversity in the world, with almost a thousand known species (Segalla et  al., 2014), the larvae of many species remain undescribed. The problem is not unique to Brazil. At the turn of the century, approximately ⅔ of almost 3,300 anuran species with a larval stage lacked tadpole descriptions (McDiarmid & Altig, 1999). The proportion of neotropical anurans with free-swimming larvae that are not described is estimated to be around 40% (Provete et al., 2012).Fil: Rossa Feres, Denise de C.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Venesky, Matthew. Allegheny College; Estados UnidosFil: Nomura, Fausto. Universidade Federal de Goias; BrasilFil: Eterovick, Paula C.. Pontifícia Universidade Católica de Minas Gerais; BrasilFil: Vera Candioti, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Menin, Marcelo. Universidade Federal do Amazonas; BrasilFil: Juncá, Flora A.. Universidade Estadual de Feira de Santana; BrasilFil: Schiesari, Luis C.. Universidade de Sao Paulo; BrasilFil: Haddad, Celio F. B.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Garey, Michel V.. Universidade Federal da Integração Latino-Americana; BrasilFil: dos Anjos, Luciano A.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Wasserug, Richard. Dalhousie University Halifax; Canadá. University Of British Columbia; Canad

Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma

Background: The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods: Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib). Results: Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment. Conclusions: Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population. Trial registration: ClinicalTrials.gov Identifier: NCT01088815

Identification and characterization of a nodH ortholog from the alfalfa-nodulating Or191-like rhizobia

Nodulation of Medicago sativa (alfalfa) is known to be restricted to Sinorhizobium meliloti and a few other rhizobia that include the poorly characterized isolates related to Rhizobium sp. strain Or191. Distinctive features of the symbiosis between alfalfa and S. meliloti are the marked specificity from the plant to the bacteria and the strict requirement for the presence of sulfated lipochitooligosaccharides (Nod factors [NFs]) at its reducing end. Here, we present evidence of the presence of a functional nodH-encoded NF sulfotransferase in the Or191-like rhizobia. The nodH gene, present in single copy, maps to a high molecular weight megaplasmid. As in S. meliloti, a nodF homolog was identified immediately upstream of nodH that was transcribed in the opposite direction (local synteny). This novel nodH ortholog was cloned and shown to restore both NF sulfation and the Nif +Fix+ phenotypes when introduced into an S. meliloti nodH mutant. Unexpectedly, however, nodH disruption in the Or191-like bacteria did not abolish their ability to nodulate alfalfa, resulting instead in a severely delayed nodulation. In agreement with evidence from other authors, the nodH sequence analysis strongly supports the idea that the Or191-like rhizobia most likely represent a genetic mosaic resulting from the horizontal transfer of symbiotic genes from a sinorhizobial megaplasmid to a not yet clearly identified ancestor.Instituto de Biotecnologia y Biologia Molecula

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis : Differences between males and females

Deficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset. The initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up. FEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = −0.307, p = 0.012) were significantly associated with functioning. Our data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended

Corrigendum : Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: differences between males and females

Deficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset. The initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up. FEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = −0.307, p = 0.012) were significantly associated with functioning. Our data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended

Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells

The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvβ3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin αvβ3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvβ3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin αvβ3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvβ3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.Fil: Cayrol, Maria Florencia. Pontificia Universidad Católica Argentina ; ArgentinaFil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina ; ArgentinaFil: Tharu, Fernando. Cornell University; Estados UnidosFil: Yang, Shao Ning. Cornell University; Estados UnidosFil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina ; ArgentinaFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Amorós, Mariana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Isse, Blanca Alicia de Los Angeles G.. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Farias, Ricardo Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Ahn, Haelee. Cornell University; Estados UnidosFil: Tian, Ye F.. Cornell University; Estados UnidosFil: Tabbò, Fabrizio. Cornell University; Estados UnidosFil: Singh, Ajnesh. Cornell University; Estados UnidosFil: Inghirami, Giorgio. Cornell University; Estados UnidosFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados UnidosFil: Cremaschi, Graciela Alicia. Pontificia Universidad Católica Argentina ; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: Differences between males and females

Background: Deficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset. Materials and methods: The initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up. Results: FEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = -0.307, p = 0.012) were significantly associated with functioning. Conclusion: Our data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended